Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone as 2nd-Line Treatment in PAC

NCT03665441 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: GRASPANC 2018-01
• Study Type: interventional
• Target: 512
• Locations: 3 countries
• Sites: 16

Brief Summary

This is an open-label, multicenter, randomized, Phase 3 study in patients with ductal adenocarcinoma of the pancreas who have failed only one prior line of systemic anti-cancer therapy for advanced pancreatic cancer and have measurable disease.

Conditions

Pancreatic Adenocarcinoma

Keywords

pancreatic; cancer; asparaginase; gemcitabine; Abraxane; asparagine depletion; onivyde; nab-paclitaxel; folinic acid; fluorouracil; irinotecan; leucovorin; amino acid; RECIST 1.1

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  To determine whether the addition of eryaspase to chemotherapy improves OS when compared to chemotherapy alone

  ~12 months

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  ~24 weeks

• Objective Response Rate (ORR)

  ~24 weeks

• Duration of Response (DoR)

  ~24 weeks

• Disease Control Rate (DCR)

  ~24 weeks

• Incidence of Treatment Emergent Adverse Events as Assessed by CTCAE v5.0

  ~9 months

Study Arms (2)

Eryaspase plus Chemotherapy

EXPERIMENTAL

eryaspase 100 U/kg dosed every 2 weeks in combination with Gemcitabine plus abraxane (albumin-bound paclitaxel) administered on Days 1, 8, and 15 of each 4 week cycle as follows: * Abraxane (125 mg/m2) IV * Gemcitabine (1000 mg/m2) IV Or Irinotecan plus 5-FU plus leucovorin administered on Days 1 and 15 of each 4 week cycle as follows: * Onivyde 70 mg/m2 (irinotecan freebase) IV (recommended dose in patients homozygous for UGT1A1\*28 is 50 mg/m2) * Leucovorin 400 mg/m2 IV * 5 FU 2400 mg/m2 Or * FOLFIRI: Irinotecan 180 mg/m2 IV * Leucovorin 400 mg/m² IV * 5 FU 400 mg/m² IV bolus * 5 FU 2400 mg/m² IV continuous infusion over 46 hours immediately following bolus 5 FU

Drug: eryaspase; Drug: Gemcitabine plus Abraxane; Drug: Irinotecan plus 5-FU plus leucovorin

Chemotherapy alone

OTHER

Standard treatment: Gemcitabine plus abraxane (albumin-bound paclitaxel) administered on Days 1, 8, and 15 of each 4 week cycle Or Irinotecan plus 5-FU plus leucovorin administered on Days 1 and 15 of each 4 week cycle

Drug: Gemcitabine plus Abraxane; Drug: Irinotecan plus 5-FU plus leucovorin

Interventions

eryaspase DRUG

L-asparaginase encapsulated in erythrocytes (red blood cells)

Also known as: L-asparaginase

Eryaspase plus Chemotherapy

Gemcitabine plus Abraxane DRUG

gemcitabine, Abraxane

Also known as: Gemzar, nab-paclitaxel, onxol

Chemotherapy alone; Eryaspase plus Chemotherapy

Irinotecan plus 5-FU plus leucovorin DRUG

irinotecan, 5-FU, leucovorin

Also known as: Onivyde, liposomal irinotecan, Camptosar, Campto, Adrucil, Carac, Efudex, Efudix, folinic acid, calcium folinate

Chemotherapy alone; Eryaspase plus Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A patient will be eligible for the study if all the following criteria are met:
• Must be 18 years of age or older.
• Must have histologically confirmed pancreatic adenocarcinoma.
• Must have Stage III or IV disease.
• Must have received one line of systemic chemotherapy in the advanced setting with or without targeted agents, immunotherapy, or radiotherapy for treatment of advanced pancreatic adenocarcinoma.
• Must have radiological evidence of disease progression following most recent prior treatment, defined as appearance of any new lesion or increase of \>20% of one or more existing lesions.
• Must have measurable lesion(s) per RECIST version 1.1 by CT scan with contrast (or MRI, if the patient is allergic to CT contrast media).
• NOTE: Bone disease consisting of blastic lesion only is not measurable.
• Archival or fresh tumor tissue must be available for evaluating relevant biomarkers. Formalin-fixed paraffin-embedded \[FFPE\] block preferred, or a minimum of 10 unstained FFPE slides of one archived block is required.
• NOTE: Cytology samples from fine needle aspirates or brushing biopsies are not sufficient.
• If archival tissue is unavailable and an elective biopsy can't be scheduled due to COVID, this will be waived.
• Must have adequate performance status:
• ECOG Performance Status (PS) score of 0, or
• ECOG PS score one and score ≥80 on Karnofsky Performance Status (KPS) scale. NOTE: Must have body mass index (BMI) ≥18.5 kg/m2 (obtained \<14 days prior to randomization.
• Must have life expectancy of \>12 weeks according to the investigator's clinical judgment.

You may not qualify if:

• A patient is not eligible to participate in the study if any of the following criteria are met:
• Resectable or borderline resectable pancreatic adenocarcinoma at the time of signing the informed consent.
• Histology other than pancreatic adenocarcinoma (for example, but not inclusive: neuroendocrine, adenosquamous, etc.).
• More than one line of prior treatment in advanced or metastatic setting.
• Patient has experienced medically significant acute decline in clinical status including
• Decline in ECOG PS to \>1 (or KPS \<70) between baseline visit and within 72 hours prior to randomization.
• Weight loss of ≥10% during screening.
• Presence of active or symptomatic untreated central nervous system (CNS) metastases.
• NOTE: Patients with asymptomatic or stable CNS metastases are eligible, provided that the CNS metastases are radiologically and clinically stable, and the patient is off high-dose steroid treatment for at least one month prior to randomization.
• Prior radiotherapy to the only area of measurable disease. NOTE: Patients must have completed treatment and recovered from all acute treatment-related toxicities prior to administration of the first dose of eryaspase or chemotherapy.
• Bone as the only site of metastatic disease from pancreatic cancer (bone only disease).
• History of recent clinical pancreatitis, according to revised Atlanta criteria, within 3 months of randomization.
• NOTE: The revised Atlanta classification \[1\] requires that two or more of the following criteria be met for the diagnosis of acute pancreatitis: (a) abdominal pain suggestive of pancreatitis, (b) serum amylase or lipase level ≥3 x ULN, or (c) characteristic imaging findings using CT or MRI.
• Neurosensory neuropathy \> Grade 2 at baseline.
• Pregnancy or breastfeeding.

Sponsors & Collaborators

• ERYtech Pharma: lead

Study Sites (16)

Arizona Cancer Center

Scottsdale, Arizona, 85258, United States

Location

St. Joseph Heritage Healthcare

Fullerton, California, 92835, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20057, United States

Location

Boca Raton Regional Hospital

Boca Raton, Florida, 33486, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Minnesota Health Clinics and Surgery Center

Minneapolis, Minnesota, 55455, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Weill Cornell Medicine

New York, New York, 10021, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Stony Brook University

Stony Brook, New York, 10021, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Medical Oncology Associates

Spokane, Washington, 99208, United States

Location

Institut de Cancerologie

Brest, 29609, France

Location

Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

Related Publications (1)

• Hammel P, Metges JP, Macarulla Mercade T, Garcia-Carbonero R, Bouche O, Portales F, Pazo Cid RA, Mineur L, Cubillo Gracian A, Trouilloud I, Guimbaud R, Tougeron D, Reina JJ, Feliu J, Sauri T, Fountzilas C, Lecomte T, Molin Y, Ponz-Sarvise M, Forget F, Berardi R, Van Cutsem E, Gelsomino F, Tournigand C, Bockorny B, Bachet JB, Marin Vera M, Cuyle PJ, Wasan H, Noel M, Van Laethem JL, Kay R, Youssoufian H, El-Hariry I, Hidalgo M. TRYBECA-1: A Randomized Phase III Study of Eryaspase Combined With Chemotherapy Versus Chemotherapy as Second-Line Treatment in Patients With Advanced Pancreatic Adenocarcinoma. J Clin Oncol. 2025 Dec 10;43(35):3714-3727. doi: 10.1200/JCO-25-00872. Epub 2025 Nov 4.

  PMID: 41187298 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

eryaspase; Asparaginase; Gemcitabine; Albumin-Bound Paclitaxel; 130-nm albumin-bound paclitaxel; Paclitaxel; Irinotecan; Fluorouracil; Leucovorin; irinotecan sucrosofate

Intervention Hierarchy (Ancestors)

Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Camptothecin; Alkaloids; Uracil; Pyrimidinones; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes

Results Point of Contact

• Title: Anu Gupta, Senior Study Team Lead
• Organization: Erytech Pharma Inc

anu.gupta@erytech.com

7327424937

Study Officials

• Manuel Hidalgo, MD, PhD

  Weill Cornell, NY, US

  PRINCIPAL INVESTIGATOR

• Pascal Hammel, MD, PhD

  Hospital Beaujon, Clichy, France

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2018
• First Posted: September 11, 2018
• Study Start: September 15, 2018
• Primary Completion: August 30, 2021
• Study Completion: January 18, 2022
• Last Updated: October 18, 2022
• Results First Posted: September 28, 2022

Record last verified: 2021-01

Locations

GB (1); US (14); FR (1)